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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2020

Open Access 01-09-2020 | Metastasis | Melanoma

Mixed Response to Immunotherapy in Patients with Metastatic Melanoma

Authors: Daan Jan Willem Rauwerdink, George Molina, MD, MPH, Dennie Tompers Frederick, MS, Tanya Sharova, MD, Jos van der Hage, MD, PhD, Sonia Cohen, MD, PhD, Genevieve Marie Boland, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2020

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Abstract

Background

Immunotherapy has improved overall survival in metastatic melanoma. Response to therapy can be difficult to evaluate as the traditionally used RECIST 1.1 criteria do not capture heterogeneous responses. Here we describe the clinical characterization of melanoma patients with a clinically defined mixed response to immunotherapy.

Methods

This was a single institution, retrospective analysis of stage IV melanoma patients who received first-line anti-CTLA-4, anti-PD1, or combination anti-CTLA-4/anti-PD1. Therapy response was assessed via clinical definitions, which consisted of cross-sectional imaging combined with clinical exam. Course of disease, clinicopathological characteristics, and management in patients with a mixed clinical response were analyzed.

Results

In 292 patients (anti-CTLA4 = 63; anti-PD1 = 148, anti-CTLA4/anti-PD1 = 81), 103 were responders (35%), 64 mixed responders (22%), and 125 patients had progressive disease (43%). Of patients with a mixed response, 56% eventually had response to therapy (mixed response followed by response, MR–R), while 31% progressed on therapy (MR–NR). MR–NR patients had higher median LDH (p < 0.01), 3 or more organ sites with metastases (p < 0.01), and more frequently had M1d disease (p < 0.01). Mixed responders who underwent surgery (n = 20) had a significantly longer mean OS compared to patients who did not undergo surgery (6.9 years, 95% CI 6.2–7.6 vs. 6.0 years, 95% CI 4.6–7.3, p = 0.02).

Discussion

Mixed response to immunotherapy in metastatic melanoma was not uncommon in our cohort (22%). Clinical characteristics associated with progression of disease after initial mixed response included higher LDH, brain metastases, and ≥ 3 organ sites with metastases. Surgical treatment for highly selected patients with a mixed response was associated with improved outcomes.
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Metadata
Title
Mixed Response to Immunotherapy in Patients with Metastatic Melanoma
Authors
Daan Jan Willem Rauwerdink
George Molina, MD, MPH
Dennie Tompers Frederick, MS
Tanya Sharova, MD
Jos van der Hage, MD, PhD
Sonia Cohen, MD, PhD
Genevieve Marie Boland, MD, PhD
Publication date
01-09-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08657-6

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